Frontline treatment with the combination obinutuzumab +/-
chlorambucil for chronic lymphocytic leukemia outside clinical
trials: Results of a multinational, multicenter study by ERIC
and the Israeli CLL study group

J 2020

Frontline treatment with the combination obinutuzumab +/- chlorambucil for chronic lymphocytic leukemia outside clinical trials: Results of a multinational, multicenter study by ERIC and the Israeli CLL study group

HERISHANU, Y., A. SHAULOV, R. FINEMAN, S. BASIC-KINDA, A. AVIV et. al.

Basic information

Original name

Frontline treatment with the combination obinutuzumab +/- chlorambucil for chronic lymphocytic leukemia outside clinical trials: Results of a multinational, multicenter study by ERIC and the Israeli CLL study group

Authors

HERISHANU, Y. (376 Israel, guarantor), A. SHAULOV (376 Israel), R. FINEMAN (376 Israel), S. BASIC-KINDA (191 Croatia), A. AVIV (376 Israel), E. WASIK-SZCZEPANEK (376 Israel), O. JAKSIC (191 Croatia), M. ZDRENGHEA (642 Romania), U. GREENBAUM (376 Israel), I. MANDAC (191 Croatia), M. SIMKOVIC (203 Czech Republic), M. MORAWSKA (616 Poland), O. BENJAMINI (376 Israel), M. SPACEK (203 Czech Republic), A. NEMETS (376 Israel), O. BAIREY (376 Israel), L. TRENTIN (380 Italy), R. RUCHLEMER (376 Israel), L. LAURENTI (380 Italy), O. S. CIOCAN (642 Romania), Michael DOUBEK (203 Czech Republic, belonging to the institution), L. SHVIDEL (376 Israel), N. DALI (376 Israel), F. MIRAS (724 Spain), A. DE METEUR (56 Belgium), M. DIMOU (300 Greece), F. R. MAURO (380 Italy), M. COSCIA (380 Italy), H. BUMBEA (642 Romania), R. SZASZ (348 Hungary), T. TADMOR (376 Israel), O. GUTWEIN (376 Israel), M. GENTILE (380 Italy), L. SCARF (380 Italy), A. TEDESCHI (380 Italy), P. SPORTOLETTI (380 Italy), E. GIMENO VAZQUEZ (724 Spain), J. MARQUET (724 Spain), S. ASSOULINE (124 Canada), M. PAPAIOANNOU (300 Greece), A. BRAESTER (376 Israel), L. LEVATO (380 Italy), M. GREGOR (756 Switzerland), G. M. RIGOLIN (380 Italy), J. LOSCERTALES (724 Spain), A. M. PEREZ (724 Spain), M. R. NIJZIEL (528 Netherlands), V. M. POPOV (642 Romania), R. COLLADO (724 Spain), I. SLAVUTSKY (32 Argentina), G. ITCHAKI (376 Israel), S. RINGELSTEIN (376 Israel), N. GOLDSCHMIDT (376 Israel), C. PERRY (376 Israel), S. LEVI (376 Israel), A. POLLIACK (376 Israel) and P. GHIA (380 Italy)

Edition

American Journal of Hematology, Hoboken, John Wiley & Sons, 2020, 0361-8609

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30205 Hematology

Country of publisher

United States of America

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 10.047

RIV identification code

RIV/00216224:14110/20:00116169

Organization unit

Faculty of Medicine

DOI

http://dx.doi.org/10.1002/ajh.25766

UT WoS

000531328600013

Keywords in English

RITUXIMAB REGIMEN; THERAPY; CYCLOPHOSPHAMIDE; FLUDARABINE; IBRUTINIB

Abstract

V originále

In recent years, considerable progress has been made in frontline therapy for elderly/physically unfit patients with CLL. The combination of obinutuzumab and chlorambucil (O-Clb) has been shown to prolong progression free survival (PFS, median PFS-31.5 months) and overall survival (OS) compared to chlorambucil alone. More recently, obinutuzumab given in combination with either ibrutinib or venetoclax improved PFS but not OS when compared to O-Clb. In this retrospective multinational, multicenter co-operative study, we evaluated the efficacy and safety of frontline treatment with O +/- Clb in unfit patients with CLL, in a "real-world" setting. Patients with documented del (17p13.1)/TP53 mutation were excluded. A total of 437 patients (median age, 75.9 years; median CIRS score, 8; median creatinine clearance, 61.1 mL/min) were included. The clinical overall response rate was 80.3% (clinical complete and partial responses in 38.7% and 41.6% of patients, respectively). Median observation time was 14.1 months and estimated median PFS was 27.6 months (95% CI, 24.2-31.0). In a multivariate analysis, high-risk disease [del (11q22.3) and/or IGHV-unmutated], lymph nodes of diameter > 5 cm, obinutuzumab monotherapy and reduced cumulative dose of obinutuzumab, were all independently associated with shorter PFS. The median OS has not yet been reached and estimated 2-year OS is 88%. In conclusion, in a "real-world" setting, frontline treatment with O-Clb achieves PFS comparable to that reported in clinical trials. Inferior outcomes were noted in patients with del (11q22.3) and/or unmutated IGHV and those treated with obinutuzumab-monotherapy. Thus, O-Clb can be still considered as legitimate frontline therapy for unfit CLL patients with low-risk disease.

Citovat

HERISHANU, Y., A. SHAULOV, R. FINEMAN, S. BASIC-KINDA, A. AVIV, E. WASIK-SZCZEPANEK, O. JAKSIC, M. ZDRENGHEA, U. GREENBAUM, I. MANDAC, M. SIMKOVIC, M. MORAWSKA, O. BENJAMINI, M. SPACEK, A. NEMETS, O. BAIREY, L. TRENTIN, R. RUCHLEMER, L. LAURENTI, O. S. CIOCAN, Michael DOUBEK, L. SHVIDEL, N. DALI, F. MIRAS, A. DE METEUR, M. DIMOU, F. R. MAURO, M. COSCIA, H. BUMBEA, R. SZASZ, T. TADMOR, O. GUTWEIN, M. GENTILE, L. SCARF, A. TEDESCHI, P. SPORTOLETTI, E. GIMENO VAZQUEZ, J. MARQUET, S. ASSOULINE, M. PAPAIOANNOU, A. BRAESTER, L. LEVATO, M. GREGOR, G. M. RIGOLIN, J. LOSCERTALES, A. M. PEREZ, M. R. NIJZIEL, V. M. POPOV, R. COLLADO, I. SLAVUTSKY, G. ITCHAKI, S. RINGELSTEIN, N. GOLDSCHMIDT, C. PERRY, S. LEVI, A. POLLIACK and P. GHIA. Frontline treatment with the combination obinutuzumab +/- chlorambucil for chronic lymphocytic leukemia outside clinical trials: Results of a multinational, multicenter study by ERIC and the Israeli CLL study group. American Journal of Hematology. Hoboken: John Wiley & Sons, 2020, vol. 95, No 6, p. 604-611. ISSN 0361-8609. Available from: https://dx.doi.org/10.1002/ajh.25766.

@article{1673752,
   author = {Herishanu, Y. and Shaulov, A. and Fineman, R. and BasicandKinda, S. and Aviv, A. and WasikandSzczepanek, E. and Jaksic, O. and Zdrenghea, M. and Greenbaum, U. and Mandac, I. and Simkovic, M. and Morawska, M. and Benjamini, O. and Spacek, M. and Nemets, A. and Bairey, O. and Trentin, L. and Ruchlemer, R. and Laurenti, L. and Ciocan, O. S. and Doubek, Michael and Shvidel, L. and Dali, N. and Miras, F. and De Meteur, A. and Dimou, M. and Mauro, F. R. and Coscia, M. and Bumbea, H. and Szasz, R. and Tadmor, T. and Gutwein, O. and Gentile, M. and Scarf, L. and Tedeschi, A. and Sportoletti, P. and Gimeno Vazquez, E. and Marquet, J. and Assouline, S. and Papaioannou, M. and Braester, A. and Levato, L. and Gregor, M. and Rigolin, G. M. and Loscertales, J. and Perez, A. M. and Nijziel, M. R. and Popov, V. M. and Collado, R. and Slavutsky, I. and Itchaki, G. and Ringelstein, S. and Goldschmidt, N. and Perry, C. and Levi, S. and Polliack, A. and Ghia, P.},
   article_location = {Hoboken},
   article_number = {6},
   doi = {http://dx.doi.org/10.1002/ajh.25766},
   keywords = {RITUXIMAB REGIMEN; THERAPY; CYCLOPHOSPHAMIDE; FLUDARABINE; IBRUTINIB},
   language = {eng},
   issn = {0361-8609},
   journal = {American Journal of Hematology},
   title = {Frontline treatment with the combination obinutuzumab +/- chlorambucil for chronic lymphocytic leukemia outside clinical trials: Results of a multinational, multicenter study by ERIC and the Israeli CLL study group},
   url = {https://onlinelibrary.wiley.com/doi/full/10.1002/ajh.25766},
   volume = {95},
   year = {2020}
}

TY  - JOUR
ID  - 1673752
AU  - Herishanu, Y. - Shaulov, A. - Fineman, R. - Basic-Kinda, S. - Aviv, A. - Wasik-Szczepanek, E. - Jaksic, O. - Zdrenghea, M. - Greenbaum, U. - Mandac, I. - Simkovic, M. - Morawska, M. - Benjamini, O. - Spacek, M. - Nemets, A. - Bairey, O. - Trentin, L. - Ruchlemer, R. - Laurenti, L. - Ciocan, O. S. - Doubek, Michael - Shvidel, L. - Dali, N. - Miras, F. - De Meteur, A. - Dimou, M. - Mauro, F. R. - Coscia, M. - Bumbea, H. - Szasz, R. - Tadmor, T. - Gutwein, O. - Gentile, M. - Scarf, L. - Tedeschi, A. - Sportoletti, P. - Gimeno Vazquez, E. - Marquet, J. - Assouline, S. - Papaioannou, M. - Braester, A. - Levato, L. - Gregor, M. - Rigolin, G. M. - Loscertales, J. - Perez, A. M. - Nijziel, M. R. - Popov, V. M. - Collado, R. - Slavutsky, I. - Itchaki, G. - Ringelstein, S. - Goldschmidt, N. - Perry, C. - Levi, S. - Polliack, A. - Ghia, P.
PY  - 2020
TI  - Frontline treatment with the combination obinutuzumab +/- chlorambucil for chronic lymphocytic leukemia outside clinical trials: Results of a multinational, multicenter study by ERIC and the Israeli CLL study group
JF  - American Journal of Hematology
VL  - 95
IS  - 6
SP  - 604-611
EP  - 604-611
PB  - John Wiley & Sons
SN  - 03618609
KW  - RITUXIMAB REGIMEN
KW  - THERAPY
KW  - CYCLOPHOSPHAMIDE
KW  - FLUDARABINE
KW  - IBRUTINIB
UR  - https://onlinelibrary.wiley.com/doi/full/10.1002/ajh.25766
L2  - https://onlinelibrary.wiley.com/doi/full/10.1002/ajh.25766
N2  - In recent years, considerable progress has been made in frontline therapy for elderly/physically unfit patients with CLL. The combination of obinutuzumab and chlorambucil (O-Clb) has been shown to prolong progression free survival (PFS, median PFS-31.5 months) and overall survival (OS) compared to chlorambucil alone. More recently, obinutuzumab given in combination with either ibrutinib or venetoclax improved PFS but not OS when compared to O-Clb. In this retrospective multinational, multicenter co-operative study, we evaluated the efficacy and safety of frontline treatment with O +/- Clb in unfit patients with CLL, in a "real-world" setting. Patients with documented del (17p13.1)/TP53 mutation were excluded. A total of 437 patients (median age, 75.9 years; median CIRS score, 8; median creatinine clearance, 61.1 mL/min) were included. The clinical overall response rate was 80.3% (clinical complete and partial responses in 38.7% and 41.6% of patients, respectively). Median observation time was 14.1 months and estimated median PFS was 27.6 months (95% CI, 24.2-31.0). In a multivariate analysis, high-risk disease [del (11q22.3) and/or IGHV-unmutated], lymph nodes of diameter > 5 cm, obinutuzumab monotherapy and reduced cumulative dose of obinutuzumab, were all independently associated with shorter PFS. The median OS has not yet been reached and estimated 2-year OS is 88%. In conclusion, in a "real-world" setting, frontline treatment with O-Clb achieves PFS comparable to that reported in clinical trials. Inferior outcomes were noted in patients with del (11q22.3) and/or unmutated IGHV and those treated with obinutuzumab-monotherapy. Thus, O-Clb can be still considered as legitimate frontline therapy for unfit CLL patients with low-risk disease.
ER  -

HERISHANU, Y., A. SHAULOV, R. FINEMAN, S. BASIC-KINDA, A. AVIV, E. WASIK-SZCZEPANEK, O. JAKSIC, M. ZDRENGHEA, U. GREENBAUM, I. MANDAC, M. SIMKOVIC, M. MORAWSKA, O. BENJAMINI, M. SPACEK, A. NEMETS, O. BAIREY, L. TRENTIN, R. RUCHLEMER, L. LAURENTI, O. S. CIOCAN, Michael DOUBEK, L. SHVIDEL, N. DALI, F. MIRAS, A. DE METEUR, M. DIMOU, F. R. MAURO, M. COSCIA, H. BUMBEA, R. SZASZ, T. TADMOR, O. GUTWEIN, M. GENTILE, L. SCARF, A. TEDESCHI, P. SPORTOLETTI, E. GIMENO VAZQUEZ, J. MARQUET, S. ASSOULINE, M. PAPAIOANNOU, A. BRAESTER, L. LEVATO, M. GREGOR, G. M. RIGOLIN, J. LOSCERTALES, A. M. PEREZ, M. R. NIJZIEL, V. M. POPOV, R. COLLADO, I. SLAVUTSKY, G. ITCHAKI, S. RINGELSTEIN, N. GOLDSCHMIDT, C. PERRY, S. LEVI, A. POLLIACK and P. GHIA. Frontline treatment with the combination obinutuzumab +/- chlorambucil for chronic lymphocytic leukemia outside clinical trials: Results of a multinational, multicenter study by ERIC and the Israeli CLL study group. \textit{American Journal of Hematology}. Hoboken: John Wiley \&{} Sons, 2020, vol.~95, No~6, p.~604-611. ISSN~0361-8609. Available from: https://dx.doi.org/10.1002/ajh.25766.

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